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Objective: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA., Methods: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies., Results: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East., Conclusion: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab's effect on achieving low disease activity or remission., Methods: In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C-reactive protein level ≥0.3 mg/dl, ≥3% body surface-area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with <5% improvement in swollen and tender joints could early escape to open-label ustekinumab. Patients continuing placebo crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 (placebo to guselkumab). PsA composite indices (Psoriatic Arthritis Disease Activity Score [PASDAS], Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score [GRACE], modified Composite Psoriatic Disease Activity Index [mCPDAI], and Disease Activity in Psoriatic Arthritis [DAPSA]) were analyzed as secondary outcomes (last observation carried forward for missing/post-early escape data through week 24; observed data post-week 24). Instrument performance was assessed., Results: Baseline PASDAS, GRACE, mCPDAI, and DAPSA scores indicated moderate-to-high disease activity. At week 24, mean changes in each of these composite indices showed significant improvement with guselkumab (-2.50, -2.73, -3.8, and -23.08, respectively) versus placebo (-0.49, 0.35, -0.8, and -4.98, respectively; P < 0.001 for all). Significantly more guselkumab-treated patients achieved low/very low/remitted disease activity states according to PASDAS (very low + low 35% versus 4%; P < 0.001), GRACE (30% versus 2%; P < 0.001), mCPDAI (46% versus 10%; P < 0.001), and DAPSA (remission + low 40% versus 12%; P < 0.001). A total of 12% of guselkumab-treated versus no placebo-treated patients achieved DAPSA remission (P < 0.01). The PASDAS and GRACE instruments were more sensitive than the mCPDAI and DAPSA tools in detecting treatment effect. Residual skin disease and enthesitis were marginally more prominent in patients achieving DAPSA low disease activity versus other indices., Conclusion: Guselkumab demonstrated efficacy in achieving low disease activity/remission based on all PsA composite indices assessed. Composite index use in PsA trials and the clinic requires careful consideration to optimize feasibility and instrument performance., (© 2019, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objectives: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria., Methods: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated., Results: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%)., Conclusions: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis (PsA). We aimed to validate a cutoff value of PASDAS that defines minimal disease activity (MDA) state, as well as to validate previously defined PASDAS cutoffs for low and high disease activity., Methods: Patients were prospectively recruited from the University of Toronto PsA clinic according to a standard protocol, and variables necessary to complete the PASDAS and the MDA were collected. Receiver-operating characteristic (ROC) curve analysis determined the optimal PASDAS cutoff discriminating patients in MDA state from those not in MDA. Previously proposed PASDAS disease activity cutoff scores were validated by determining the proportion of patients requiring treatment escalation, a surrogate of active disease, in each of low, moderate, and high disease activity groups., Results: One hundred seventy-eight patients [53.9% male, mean PASDAS 3.29 (SD 1.29), 47.8% in MDA] were recruited. ROC curve analysis identified a PASDAS score of 3.2 as the point that maximized the sensitivity and specificity for MDA based on 5 of 7 criteria (sensitivity 88%, specificity 92%, area under the curve 0.96). For MDA based on meeting 6 of 7 and 7 of 7 criteria, PASDAS scores of 2.6 and 2.1 maximized sensitivity and specificity, respectively. An increasing proportion of patients from low to moderate to high disease activity groups required treatment escalation, increasing from 8.1% to 42% to 67%, respectively., Conclusion: A PASDAS score < 3.2 reflects MDA. This study has externally validated PASDAS cutoff scores previously proposed to differentiate between low, moderate, and high disease activity.

Objective: To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort., Methods: The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values., Results: The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21., Conclusion: The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.

Objective: To evaluate the properties of a frailty index (FI), constructed using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, as a novel health measure in systemic lupus erythematosus (SLE)., Methods: For this secondary analysis, the baseline visit was defined as the first study visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36] scores) were assessed. The SLICC-FI was constructed using baseline data. The SLICC-FI comprises 48 health deficits, including items related to organ damage, disease activity, comorbidities, and functional status. Content, construct, and criterion validity of the SLICC-FI were assessed. Multivariable Cox regression was used to estimate the association between baseline SLICC-FI values and mortality risk, adjusting for demographic and clinical factors., Results: In the baseline data set of 1,683 patients with SLE, 89% were female, the mean ± SD age was 35.7 ± 13.4 years, and the mean ± SD disease duration was 18.8 ± 15.7 months. At baseline, the mean ± SD SLICC-FI score was 0.17 ± 0.08 (range 0-0.51). Baseline SLICC-FI values exhibited the expected measurement properties and were weakly correlated with baseline SDI scores (r = 0.26, P < 0.0001). Higher baseline SLICC-FI values (per 0.05 increment) were associated with increased mortality risk (hazard ratio 1.59, 95% confidence interval 1.35-1.87), after adjusting for age, sex, steroid use, ethnicity/region, and baseline SDI scores., Conclusion: The SLICC-FI demonstrates internal validity as a health measure in SLE and might be used to predict future mortality risk. The SLICC-FI is potentially valuable for quantifying vulnerability among patients with SLE, and adds to existing prognostic scores., (© 2019, American College of Rheumatology.)

Objective: We aimed to determine the agreement between rheumatologist-judged inflammatory back pain (IBP) and criteria defining IBP in patients with psoriatic arthritis (PsA) and predictive value of IBP in identifying axial involvement in PsA., Methods: Using prospectively collected data, we investigated the agreement between rheumatologist judgement of IBP and IBP criteria (Calin, Rudwaleit and Assessment of Spondyloarthritis International Society) using the kappa coefficient. We also determined the sensitivity, specificity and likelihood ratios of the presence of back pain, rheumatologist-judged IBP and the three IBP criteria for detecting axial PsA (AxPsA). Finally, we compared the clinical and genetic markers in patients with PsA with axial radiological changes with and without back pain., Results: 171 patients (52% male, mean age 46.6 years) were identified. Ninety-six (56.13%) patients reported chronic back pain. Sixty-five (38.01%) had IBP. 54 (32%) patients had evidence of radiological change in the spine. The agreement between rheumatologist judgement of IBP and IBP criteria was highest for the Calin criteria (0.70). Positive likelihood ratio for the presence of radiological axial involvement was highest for Rudwaleit criteria (2.17). No differences between patients with AxPsA with or without back pain were found, except for higher Bath Ankylosing Spondylitis Disease Activity Index and lower prevalence of human leucocyte antigen-B*38 in those with back pain., Conclusion: Rheumatologist-judged IBP or the criteria for IBP developed for ankylosing spondylitis may not perform well when ascertaining axial involvement in PsA., Competing Interests: Competing interests: KSY was supported by a Ken Muirden Scholarship from Arthritis Australia., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field., Competing Interests: Competing interests: DA served as a consultant and/or speaker for Abbvie, Astra-Zeneca, BMS, Janssen, Medac, MSD, Pfizer, Roche, UCB and received grant support from BMS. XB has served as consultant and/or speaker for Abbvie, BMS, Celgene, Chugai, Janssen, Novartis, Pfizer, UCB. NB has received consultancy fees for work commissioned by Grünenthal, Lilly, Janssen, PfizerLaura Coates has received research funding from Abbvie and Janssen and honoraria from Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, UCBMaxime Dougados has participated as a speaker in symposia or as an advisor in boards organized by Pfizer, Abbvie, Ucb, Merck, Amgen, Novartis, Lilly, Bms, Roche and his department has received research grants from Pfizer, Abbvie, Ucb, Merck, Amgen, Novartis, Lilly, Bms, Roche. Laure Gossec has received honoraria or research funding from Abbvie, BMS, Celgene, Janseen, MSD, Novartis, Pfizer, Roche and UCB. PE has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. OF reports grants and personal fees from Novartis, personal fees from Pfizer, personal fees from Lilly, personal fees from Cellgene, grants and personal fees from Abbvie, personal fees from Janssen, personal fees from UCB, outside the submitted work. AK has served as consultant and/or performed clinical research for Abbvie, Amgen, Celgene, Janssen, Novartis, UCB. PMM has received consultancy/speaker’s fees from AbbVie, Centocor, Janssen, Merck, Novartis, Pfizer and UCB. AM has received honoraria from Abbvie, MSD and UCBDP has received Grant/research support from: AbbVie, MSD, Novartis, Pfizer, has honoraria/speaker fees from AbbVie, BMS, Boehringer, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB. MR has received honoraria/ consultancies from Abbvie, BMS, Celgene, Chugai/Roche, Janssen, MSD, Novartis, Pfizer, UCB. JS has received grant support from and/or provided expert advice to Abbvie, Amgen, Astra-Zeneca, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Gilead, Glaxo, Iltoo, Janssen, Lilly, Pfizer, MSD, Roche, Samsung, Novartis-Sandoz, UCB. TS has received honoraria from Abbvie, Janssen, MSD, Novartis and Roche and grant support from Abbvie. FVB has received speaker and/or consultancy fees from AbbVie, Celgene, Janssen,Lilly, MSD, Novartis, Pfizer and UCB. DH has received consulting fees Afrom bbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, and is Director of Imaging Rheumatology bv. MW has received consulting fees for lectures or advisory board meetings from Abbvie, BMS, Celgene, Eli Lilly, Novartis and Roche., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: There is no widely recognized method used to assess axial disease in psoriatic arthritis (PsA). We aimed to determine the sensitivity to change of the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s), the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), the Radiographic Ankylosing Spondylitis Spine Score (RASSS), and the PsA Spondylitis Radiology Index (PASRI) in axial PsA., Methods: Radiographs of 105 patients with axial PsA were retrieved for 2 time points at least 2 years apart and subsequently anonymized. All radiographs were scored by 3 rheumatologists blinded to name and order of examination using an electronic application that allowed recording of disease manifestations specific to axial PsA and automatically calculated the BASRI-s, mSASSS, RASSS, and PASRI scores. An independent expert determined whether there was true radiographic progression from an overall impression after viewing the radiographs with knowledge of chronologic order. The sensitivity, specificity, and odds ratios for every 1-unit increase in the scores were determined to identify true change., Results: Of the patients studied, 25 (24%) showed progression, as determined by the independent expert. The respective sensitivity and specificity values for an increase in score to detect true change were as follows: 0.48 and 0.78 (BASRI-s), 0.52 and 0.84 (mSASSS), 0.44 and 0.84 (RASSS), and 0.52 and 0.74 (PASRI). Logistic regression analyses showed that an increase of 1 point in the respective scores was associated with the following odds ratios for identifying true progression: BASRI-s 3.0, mSASSS 5.27, RASSS 3.70, and PASRI 3.06., Conclusion: Available scoring systems for quantifying radiographic axial PsA have moderate sensitivity but high specificity for detecting true change., (© 2017, American College of Rheumatology.)

Objective: To define and identify a group of systemic lupus erythematosus patients with low disease activity (LDA) and to examine whether LDA is similar to patients in remission and different from a high disease activity group (HDA) in short-term outcomes., Methods: The LDA group was defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <3, including only 1 clinical manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis, fever, thrombocytopenia, or leukopenia. The patients could be taking antimalarials. Remission was defined as no clinical manifestation from taking antimalarials alone, and the HDA group was defined as SLEDAI-2K >6. The time frame for inclusion in each group was at least 1 year., Results: Of 620 patients with active disease who were seen between 1970 and 2015, 80 patients (12.9%) fulfilled the criteria for LDA, 191 (30.8%) for remission, and 349 (56.3%) for HDA. The LDA patients with and without positive serology results were similar at baseline and with prior disease characteristics. After 2 years of followup, the LDA and remission groups were similar in their adjusted mean SLEDAI-2K score, organ involvement, The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score, mortality, and therapies. After 2 and 4 years of followup, the HDA group had a higher adjusted mean SLEDAI-2K score, more major organ involvement, a higher SDI score, higher mortality, and more therapy compared to the combined LDA/remission groups., Conclusion: LDA and remission groups had similar short-term outcomes, and both had better outcomes and prognosis than the HDA group. LDA may be used as an outcome measure in therapeutic trials or in treat-to-target regimens., (© 2016, American College of Rheumatology.)

Objective: To develop new composite disease activity indices for psoriatic arthritis (PsA)., Methods: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28)., Results: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures., Conclusions: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Aim: To compare the extent of atherosclerosis in patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis without arthritis (PsC)., Methods: In this cross-sectional study the authors compared patients with PsA with PsC patients. Psoriasis patients underwent a rheumatological assessment to exclude inflammatory arthritis. Ultrasonographic measurements of carotid total plaque area (TPA) and carotid intima-media thickness (cIMT) were performed. t Test was used to compare the imaging findings between the two groups. Multivariate linear regression analysis was used to assess the association between disease status and imaging findings after adjusting for potential confounders., Results: Overall, 125 PsA and 114 PsC patients were compared. There were no significant differences in age, gender or cardiovascular risk factors between the two groups. Patients with PsA exhibited greater TPA than did PsC patients (TPA (square root of area in mm(2)) 3.33±3.34 vs 2.43±2.72, p=0.03). This difference remained statistically significant in the multivariate regression analysis after adjusting for potential confounders (p=0.03). The difference in cIMT between the groups did not achieve statistical significance (p=0.09). The following disease-related variables were associated with increase in TPA in multivariate regression analysis among PsA patients: duration of PsA (p=0.04), highest Psoriasis Area and Severity Index recorded in the first 3 years of follow-up (p=0.02) and erythrocyte sedimentation rate (p=0.005)., Conclusions: PsA patients suffer from more severe subclinical atherosclerosis compared with patients with PsC. This difference is independent of traditional cardiovascular risk factors and correlates with PsA disease duration, more severe skin disease and increased inflammatory markers.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) established the GRAPPA Composite Exercise (GRACE) to compare existing and emerging composite disease activity and responder measures. At the GRAPPA 2010 annual meeting, initial results from this project were presented, and voting on available measures took place. At the GRAPPA 2011 meeting, further comparisons of new and existing measures were made, along with an outline plan for further work.

Objectives: To determine whether there is seasonal variation in disease activity of patients with psoriatic arthritis (PsA)., Methods: The authors identified the first available set of consecutive summer and winter visits for every patient from the prospective cohort of PsA. Comparison between summer and winter visits, and comparison of the repeated summer/winter visits, from 1978 until 2011 for the same identified patients was conducted for demographics, disease activity outcomes, laboratory results and treatment. The authors categorised disease activity into high, moderate and low states, and improvement versus flare/worsening. Descriptive statistics were computed and multivariate analyses using logistic regression and generalised estimating equations were conducted., Results: The first available summer and winter visit were identified for 253 patients, and 1789 observations were analysed. There was no statistically significant difference in patients' demographics, disease activity outcomes, laboratory results and treatment between summer and winter visits. Bath Ankylosing Spondylitis Disease Activity Index scores were greater for summer visits and patients graded their disease as being worse in winter as compared with summer in the univariate analysis, but this difference did not hold in the multivariate analysis., Conclusions: The change in season does not affect PsA patients' characteristics and disease activity outcomes as determined by the physicians and patients.

Objective: Neuropsychiatric (NP) manifestations attributable to active disease affect up to 30% of individuals with systemic lupus erythematosus (SLE). The short-term impact of NP events includes increased organ damage, fatigue, and mortality, and lower health-related quality of life. We investigated the impact of NP events attributable to active SLE at presentation on long-term disease activity, organ damage, and health-related quality of life., Methods: Seventy-two NP cases and 144 matched controls from the University of Toronto Lupus Cohort, enrolled between 1970 and 2005, were included in the study. NP cases had at least 1 NP event attributable to active SLE at the first clinic visit. Controls did not have NP events at the first clinic visit and were matched to cases on age, sex, disease duration, and decade. Paired case-control analyses were performed on measures of disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000), disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and health-related quality of life (Short Form 36) at 1 year, 3 years, and 5 years after the first clinic visit., Results: NP cases showed greater disease activity than controls at the first clinic visit (P < 0.0001) and greater cumulative organ damage at 1-year followup (P = 0.01). No statistically significant differences were found on 3-year or 5-year outcomes. Mean scores showed a decreasing trend of disease activity, increasing organ damage, and persistently low quality of life for both cases and controls., Conclusion: This study shows that early NP events due to active SLE are not major contributors to long-term disease activity, accumulation of damage, or health-related quality of life. The long-term prognosis and patterns of disease in SLE patients with early NP events are similar to those of SLE patients without these events., (Copyright © 2012 by the American College of Rheumatology.)

Objective: PsA is an inflammatory arthritis present in ∼30% of people with psoriasis (PsC). Both conditions have a significant impact on quality of life (QoL). Our objective was to test the hypothesis that people with PsA have poorer QoL than patients with PsC because of the added burden of arthritis, age and comorbidities., Methods: Consecutive patients with PsA (CASPAR criteria) and PsC were approached to participate in this study. Patients with PsC were examined by a rheumatologist using a standardized protocol to exclude PsA. Patients completed the HAQ, Medical Outcome Study 36-item Short Form Health Survey, Dermatology Life Quality Index (DLQI), EuroQoL 5 domains (EQ-5D) and Fatigue Severity Scale (FSS). Mean scores were compared and multivariate analyses were conducted to compare the QoL measures between the two patient groups., Results: Two hundred and one patients with PsC and 201 patients with PsA were studied. A significant decrease in QoL for patients with PsA compared with those with PsC was identified by all questionnaires except for the DLQI. This skin-specific questionnaire revealed a lower QoL in patients with PsC. Multivariate analyses for each QoL measure confirmed the results of these analyses. After adjusting for age, sex, duration of PsC, comorbidities, DMARDs and biologic therapy, HAQ and DLQI were independently associated with PsA in a logistic regression., Conclusion: Patients with PsA have a poorer QoL compared with those with PsC as measured by all questionnaires except the DLQI.

Objective: To evaluate the effect of pregnancy on ankylosing spondylitis (AS)., Methods: Our study aimed to determine the severity of back pain and stiffness pre-, during, and postpartum in patients with AS and controls, and corresponding extraarticular symptoms., Results: Nineteen female patients with AS (35 pregnancies) and 33 controls (77 pregnancies) were studied. Improvement in pain was reported in 51% of AS patients, predominantly in the first trimester, with significant improvement in pain than stiffness. In both groups, pain worsened in later stages, likely secondary to biomechanical loading. Postpartum pain scores in AS returned to prepartum levels in general., Conclusion: Pregnancy does not substantially aggravate disease activity or severity in AS.

Objective: To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders., Methods: Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician's Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50., Results: A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001)., Conclusion: SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

Work within the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) to develop and validate composite disease activity measures in PsA has progressed. At the Outcome Measures in Rheumatology Clinical Trials (OMERACT) 8 meeting, a core set of domains to be assessed in randomized controlled trials (RCT) and longitudinal observational studies (LOS) of PsA was agreed upon. At OMERACT 10, work to date regarding proposed composite responder indices was presented. Five proposed composite responder definitions for PsA were reviewed and discussed including new data from the GRACE (GRAppa Composite Exercise) study. There was agreement that the work to date was promising, and that developing composite outcome measures for use in RCT and LOS was important. Further work was required, including data on followup timepoints and less common phenotypes of PsA, to ensure that all subgroups were represented within GRACE. During discussion on the concept of composite measures for PsA, based on predominant/little/no involvement in several domains (such as skin versus joints, enthesitis, dactylitis, spondyloarthritis) it was acknowledged that a simple summative score encompassing all domains of PsA would be difficult to construct psychometrically and may not be appropriate. Ideally, any composite measure should retain the ability to differentiate between activity in individual domains, such as enthesitis or skin psoriasis, so that the influence of each can be assessed independently. Further work is required within the GRACE dataset to develop an optimal composite measure for PsA. Several proposals to date have shown preliminary validity according to the OMERACT filter.

Objective: During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA)., Methods: In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 ± 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (W0) and after 1 week (W1). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded., Results: Comparison of W0 and W1 scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38)., Conclusion: PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed.

Objective: adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine optimal visit frequency for calculating AMS., Methods: patients followed monthly for 12 consecutive visits were included. AMS was calculated using all of the SLEDAI 2000 (AMS(GOLD) using all 12 visits), only quarterly visits (AMS(3), using visits 3 months apart), semiannual visits (AMS(6), using first, middle, and last visits only), and annual visits (AMS(12), using only the first and last visits). Comparisons of AMS(3), AMS(6), and AMS(12) with AMS(GOLD) are made using descriptive statistics., Results: seventy-eight patients were included (92% women, mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD) AMS(GOLD) for the entire year was 2.05 (1.66), for AMS(3) 1.99 (1.65), for AMS(6) 2.12 (1.87), and for AMS(12) 2.08 (1.83). Mean (SD) of the absolute differences with AMS(GOLD): for AMS(3) 0.29 (0.33), for AMS(6) 0.45 (0.59), and for AMS(12) 0.61 (0.58). Differences that were < 0.5 were considered minimal while those ≥ 1 were deemed important. Comparing AMS(GOLD) to AMS(3), 82% of the differences were minimal and 3% were important. When comparing to AMS(6), 68% were minimal and 10% were important, while comparing to AMS(12), 50% were minimal and 21% were important., Conclusion: usual clinic visits occurring quarterly offer a good estimation of disease activity over a 1-year period and are preferred over semiannual and annual visits.

Objective: To develop a recommended measure of response for use in psoriatic arthritis (PsA) clinical trials and observational cohort studies reflecting joint involvement., Methods: Previously, we used data from phase III randomized placebo-controlled trials of anti-tumor necrosis factor (TNF) agents to determine models, based primarily on statistical considerations but with some clinical input when necessary, that best distinguish drug-treated from placebo-treated patients. For the same data, we examine response criteria currently used for PsA and logistic regression models based on the individual components of these response criteria. Comparison with our previously developed models, based primarily on statistical consideration, is made., Results: A simplified score, the PsA Joint Activity Index (PsAJAI), based on components of the ACR30, performed better than the ACR20 and PsARC, and comparable to our previously developed models. The PsAJAI is a weighted sum of 30% improvement in core measures with weights of 2 given to the joint count measure, the C-reactive protein laboratory measure, and the physician global assessment of disease activity measure. Weights of 1 should be given to the remaining 30% improvement measures including pain, patient global assessment of disease activity, and the Health Assessment Questionnaire., Conclusion: We recommend the PsAJAI be used as an outcome measure for assessing joint disease response in PsA clinical trials.

Objective: To assess the discriminative ability and correlation of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Activity Disease Activity Index (BASDAI) with disease activity in axial psoriatic arthritis (AxPsA)., Methods: Patients with AxPsA were selected from a large prospective cohort study of psoriatic arthritis. Patient and physician global scores were used as constructs of disease activity. Patients were categorised into high and low disease activity states based on patient and physician global assessment scores and physician's decision to change treatment. Statistical analysis included descriptive statistics, linear and logistic regression., Results: 201 patients with AxPsA were included in the study. ASDAS and BASDAI showed good correlation with disease activity as reflected by the patient global score (correlation coefficients (r) for BASDAI 0.84, ASDAS-B 0.77, ASDAS-C 0.81, p < 0.001) and the physician global score (r = 0.53 for BASDAI, r = 0.50 for ASDAS-B, r = 0.55 for ASDAS-C, p < 0.001). Both scores showed good discriminative ability between high and low disease activity states. However, there were no significant differences between areas under the curve for the models that compared ASDAS with BASDAI for each definition of disease activity state., Conclusions: In patients with AxPsA, ASDAS and BASDAI scores show similar good to moderate discriminative ability and correlation with different constructs of disease activity. ASDAS was not superior to BASDAI in its ability to discriminate between high and low disease activity states in AxPsA.

Objective: To establish the frequency and predictors of minimal disease activity in psoriatic arthritis (PsA) and to investigate the prognostic ability of minimal disease activity criteria to predict future joint damage., Methods: The study was conducted using an observational PsA cohort. Patients were classified as being in minimal disease activity if they fulfilled the criteria on consecutive visits for >12 months. Predictive factors for minimal disease activity and joint damage were investigated using regression models. Joint damage progression was based on clinically damaged joint counts., Results: Of the 344 patients, 208 (60%) achieved minimal disease activity at > or = 1 visit and 116 (34%) achieved minimal disease activity for > or = 12 months (sustained minimal disease activity). The average duration of minimal disease activity was 28 months (range 12-48 months). Twelve patients (10%) experienced a flare of disease after 34 months in minimal disease activity. Low erythrocyte sedimentation rate (ESR) and oligoarthritis were predictors of achieving sustained minimal disease activity (P < 0.03). The mean change in damaged joint counts was 0.931 (range 0-12) in the sustained minimal disease activity group and 2.245 (range 0-17) in the controls (P < 0.001). Of the sustained minimal disease activity group, 69% showed no progression of joint damage, compared with 51% in the control group. Elevated ESR, baseline joint damage, and use of biologic therapies increased the likelihood of damage progression (P < 0.05)., Conclusion: Minimal disease activity was achieved by a significant proportion of patients and was sustained in one-third of the population studied. Patients achieving sustained minimal disease activity had a significant reduction in joint damage progression. Other factors, representing disease activity and disease severity, impact on the likelihood of achieving sustained minimal disease activity and on damage progression.

At the 2008 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) in Leeds, UK, members discussed the value and current status of composite measures for the assessment of psoriatic arthritis (PsA). In plenary presentations, examples of composite measures developed for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were reviewed, followed by a presentation of the assessment of disease activity in systemic lupus erythematosus. Three recently devised composite methods of assessing activity or response in PsA also were presented. Considerable discussion followed in breakout groups, and members agreed that a new composite measure specifically for PsA is necessary. The composite measure should include components that encompass the spectrum of psoriatic disease, i.e., in addition to assessment of peripheral joints, it should include assessment of sacroiliitis, spondylitis, enthesitis, and dactylitis, as well as skin and nail disease.

Objective: Clinical trials in psoriasis and psoriatic arthritis (PsA) involve assessment of the skin and joints. This study aimed to determine whether assessment of the skin and joints in patients with PsA by rheumatologists and dermatologists is reproducible., Methods: Ten rheumatologists and 9 dermatologists from 7 countries met for a combined physical examination exercise to assess 20 PsA patients (11 men, mean age 51 years, mean PsA duration 11 years). Each physician assessed 10 patients according to a modified Latin square design that enabled the assessment of patient, assessor, and order effect. Tender joint count (TJC), swollen joint count (SJC), dactylitis, physician's global assessment (PGA) of PsA disease activity (PGA-PsA), psoriasis body surface area (BSA), Psoriasis Area and Severity Index (PASI), Lattice System Physician's Global Assessment of psoriasis (LS-PGA), National Psoriasis Foundation Psoriasis Score (NPF-PS), modified Nail Psoriasis Severity Index (mNAPSI), number of fingernails with nail changes (NN), and PGA of psoriasis activity (PGA-Ps) were assessed. Variance components analyses were carried out to estimate the intraclass correlation coefficient (ICC), adjusted for the order of measurements., Results: There is excellent agreement (ICC >/=0.80) on the mNAPSI, substantial agreement (0.6 >/= ICC < 0.80) on the TJC, PASI, and NN, moderate agreement (0.4 >/= ICC < 0.60) on the PGA-Ps, LS-PGA, NPF-PS, and BSA, and fair agreement (0.2 >/= ICC < 0.40) on the SJC, dactylitis, and PGA-PsA. The only measure that showed a significant difference between dermatologists and rheumatologists was dactylitis (P = 0.0005)., Conclusion: There is substantial to excellent agreement on the TJC, PASI, NN, and mNAPSI among rheumatologists and dermatologists.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis, with an indolent and progressive course. A delay in diagnosis and treatment may lead to an erosive arthropathy, leading further to physical disability and deformity. To help clinicians screen for PsA, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has led an effort to develop and validate 3 PsA screening tools. Administration of a well designed screening tool can increase detection of PsA, help determine the prevalence of PsA in a given population, record clinical data for genotype-phenotype studies, and track response to therapy. The development and validation of these screening tools was a major focus at the GRAPPA annual meeting at Boston in September 2007; we summarize that portion of the meeting.

Objective: To develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index., Methods: Abstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index., Results: The renal activity score was computed as follows: proteinuria 0.5-1 gm/day (3 points), proteinuria 0.5-1 gm/day = 3 points, proteinuria >1-3 gm/day = 5 points, proteinuria >3 gm/day = 11 points, [corrected] urine red blood cell count > = 5/hpf = 3 points, [corrected] urine white blood cell count > or = 5/hpf = 1 point. [corrected] The chance-adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59-0.79)., Conclusion: Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings.

Objective: To assess the degree to which physicians agree with each other and with ratings obtained with 3 existing responder indices, in rating the response to treatment of lupus nephritis., Methods: Lupus nephritis patient medical records from 125 pairs of visits (6 months apart) were used to create renal response scenarios. Seven nephrologists and 22 rheumatologists rated each scenario as demonstrating complete response, partial response, same, or worsening. The plurality (most frequent) rating of renal response by the physicians was compared with the calculated score from the renal component of the British Isles Lupus Assessment Group (BILAG) index (original and updated [2004] version) and of the Responder Index for Lupus Erythematosus (RIFLE). The degree of agreement among the physicians was assessed by calculating intraclass correlation coefficients (ICCs). The degree of agreement between the plurality physician rating and ratings obtained with the established response indices was assessed using the kappa statistic., Results: The ICC among all physicians was 0.64 (0.62 for nephrologists and 0.67 for rheumatologists). The chance-adjusted measure of agreement (kappa coefficient) between the plurality physician rating and the calculated score obtained using established indexes was 0.50 (95% confidence interval [95% CI] 0.38-0.61) for the RIFLE, 0.14 (95% CI 0.03-0.25) for the original BILAG, and 0.23 (95% CI 0.21-0.44) for the BILAG 2004., Conclusion: These findings indicate that rheumatologists as a group and nephrologists as a group have equal agreement in their rating of renal response. There was moderate agreement between plurality physician ratings and ratings obtained using the renal component of the RIFLE. Ratings of response using an index based on the original BILAG did not have good agreement with the plurality physician rating.

Objective: To investigate potential differences between childhood-onset and adult-onset systemic lupus erythematosus (SLE)., Methods: An inception cohort with childhood-onset SLE (n = 67) was compared with an inception cohort with adult-onset SLE (n = 131), each of whom was diagnosed between 1990 and 1998 and followed up until February 1999. Prospective information included data on medications, laboratory markers, and disease activity and damage as measured by the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), respectively., Results: Eighty-five percent of patients with childhood-onset SLE and 88% of patients with adult-onset SLE were female; the mean duration of followup was 3.2 and 3.5 years, respectively. On average, the children had more-active disease than did the adults at the time of diagnosis and during followup. There was a higher incidence of renal disease in those with childhood-onset SLE (78% versus 52% in adults; P = 0.0005), and the adjusted mean SLEDAI renal score was higher in the children than in the adults (2.37 versus 0.82; P < 0.0001). Treatment with steroids (97% versus 72%; P < 0.0001) and immunosuppressive drugs (66% versus 37%; P = 0.0001) was used significantly more often in children with SLE. Four adult patients with SLE, but none of the children, died during the followup. At the end of the followup, the mean SDI scores in those with childhood-onset SLE were higher than those with adult-onset SLE (1.70 versus 0.76; P = 0.008)., Conclusion: Children with childhood-onset SLE have more active disease at presentation and over time than do adults with SLE, especially active renal disease. Compared with adults with SLE, children receive more intensive drug therapy and accrue more damage, often related to steroid toxicity.

Objective: To determine the frequency of prolonged remission in systemic lupus erythematosus (SLE) using strict criteria for remission and to define disease characteristics and prognosis of patients achieving this state. To also determine the frequency of remission utilizing less restrictive definitions, such as allowing shorter period of disease quiescence, persistence of serological activity, or treatment in the absence of clinical disease., Methods: Patients registered in the Lupus Clinic database between 1970 and 1997 with visits no more than 18 months apart were identified. Prolonged remission was defined as a 5-year consecutive period of no disease activity (SLE disease activity index, SLEDAI = 0) and without treatment (corticosteroids, antimalarials, or immunosuppressants). Prolonged serologically active, clinically quiescent (SACQ) was defined as active serology (elevated anti-dsDNA by Farr assay or hypocomplementemia) but no clinical activity on SLEDAI and no treatment., Results: Seven hundred and three patients fulfilled inclusion criteria. Of the 703 patients 46 (6.5%) achieved complete remission for at least 1 year, whereas only 12 patients (1.7%) had prolonged complete remission of at least 5 years on no treatment. Although the frequency of disease manifestations was similar to the patients not in remission, the 5-year remission group was distinguished by lower overall disease activity as measured by adjusted mean SLEDAI, lower prevalence of anti-DNA antibodies, and lower use of steroids and antimalarials., Conclusion: Prolonged complete remission in lupus is rare. Therefore with current therapies continued vigilance for disease recurrence is necessary.

Objective: To test the predictability of the adjusted mean Systemic Lupus Erythematosus Disease Activity Index-2K (AMS) for main outcomes in systemic lupus erythematosus (SLE), namely presence of damage, coronary artery disease (CAD), and avascular necrosis (AVN)., Methods: Included in this study are patients with regular followup from the University of Toronto Lupus Clinic. This was defined as a minimum of 3 visits and no absence exceeding 18 consecutive months. For each visit, AMS was evaluated. The ability of the AMS to predict each of the main outcomes was evaluated through time-dependent covariate survival analysis. Adjustments to the regression models were made to include other risk factors such as sex, age at diagnosis (AGE), SLEDAI-2K at presentation (SLEDAI), disease duration (DD), and use of corticosteroids, immunosuppressives (IM), or antimalarials (AM)., Results: Five hundred and seventy-five patients were included covering the period from 1970 to 2002. A total of 325 developed damage, 55 had CAD, and 68 had AVN. Presence of damage was not associated with sex, SLEDAI, or AM but was significantly associated with AMS, AGE, DD, and use of steroids or IM (all p < 0.001). CAD was not associated with SLEDAI or use of steroids or AM but with all other variables AMS (p = 0.046), sex (p = 0.009), AGE (p < 0.0001), DD (p < 0.0001), and IM (p = 0.035). Predictors of AVN were DD (p = 0.032) and IM (p < 0.0001) but not sex, AGE, use of steroids, AM, SLEDAI, or AMS., Conclusion: AMS is associated with the presence of damage and CAD. It is not associated with AVN.

Objective: To develop Systemic Lupus International Collaborating Clinics/American College of Rheumatology Disease Damage Index (SLICC/ACR-DI) item weightings that improve the ability of the measure to predict patient mortality in systemic lupus erythematosus (SLE)., Methods: Disease damage was measured for 738 patients followed at the University of Toronto Lupus Clinic since diagnosis. Using Rasch analysis, item weightings were determined and tested for their ability to predict death in a logistic regression model. Receiver operating characteristic (ROC) curves were produced to compare the original and weighted scales' ability to discriminate patients that died during the followup period from those who remained alive., Results: The average SLICC/ACR-DI score per patient was 1.66. In total, 138 of the patients died during a mean followup of 9.2 years. A Rasch analysis derived weighting scheme using weighted domain scores (SLICC/ACR-DI-weighted) was the best weighted scale, with item reliability = 94%, model mean square infit = 1.01 (STD = 0.05); model mean square outfit = 0.99 (STD = 0.3), separation 4.08. The SLICC/ACR-DI-weighted was modestly better than the SLICC/ACR-DI in discriminating patients who died from those who remained alive. Using standardized scores for comparability, the SLICC/ACR-DI-weighted was better in predicting patient death than the unweighted SLICC/ACR-DI [OR(death)(SLICC/ACR-DI-weighted) = 1.7 vs OR(death)(SLICC-ACR-DI) = 1.4; p < 0.005]. ROC curve analysis supports that the SLICC/ACR-DI-weighted was somewhat superior to the SLICC/ACR-DI for predicting mortality., Conclusion: In this test set, the SLICC/ACR-DI-weighted was modestly better in predicting death than the traditional unweighted SLICC/ACR-DI. However, the SLICC/ACR-DI-weighted is more difficult to apply and the weightings appear not to have provided a clinically relevant improvement of the SLICC-ACR-DI.

Objective: To describe the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), a modification of SLEDAI to reflect persistent, active disease in those descriptors that had previously only considered new or recurrent occurrences, and to validate SLEDAI-2K against the original SLEDAI as a predictor for mortality and as a measure of global disease activity in the clinic., Methods: All visits in our cohort of 960 patients were used to correlate SLEDAI-2K against the original SLEDAI, and the whole cohort was used to validate SLEDAI-2K as a predictor of mortality. A subgroup of 212 patients with SLE followed at the Lupus Clinic who had 5 regular visits, 3-6 months apart, in 1991-93 was also included. An uninvolved clinician evaluated each patient record and assigned a clinical activity level. The SLEDAI score was calculated from the database according to both the original and modified definitions., Results: SLEDAI-2K correlated highly (r = 0.97) with SLEDAI. Both methods for SLEDAI scoring predicted mortality equally (p = 0.0001), and described similarly the range of disease activity as recognized by the clinician., Conclusion: SLEDAI-2K, which allows for persistent activity in rash, mucous membranes, alopecia, and proteinuria, is suitable for use in clinical trials and studies of prognosis in SLE.

BackgroundWe aimed to identify factors associated with a significant reduction in SLE disease activity over 12 months assessed by the BILAG Index.MethodsIn an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12 months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5 mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models.Results'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use.ConclusionBaseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates.

ObjectiveThe Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort.MethodsBaseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics.ResultsThe 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]).ConclusionThe SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

ObjectiveThe Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort.MethodsThe baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics.ResultsThe 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents.ConclusionOur findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.

ObjectiveTo determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients.MethodsPatients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate.ResultsOf 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy.ConclusionPNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

ObjectivesTo assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications.MethodsThis observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication.ResultsA total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)].ConclusionCHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

ObjectiveIn cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.MethodsWe included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively.ResultsCompared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01).ConclusionThe performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

Objective: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. Methods: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL‐23) pathway (IL‐17A, β‐defensin [BD‐2], and IL‐19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed. Results: IL‐17A, BD‐2, and IL‐19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL‐17A, BD‐2, IL‐19, C‐X‐C motif ligand 9 (CXCL9), CXCL10, C‐reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL‐23 pathway–associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib‐treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL‐17A (odds ratio 15.76) and BD‐2 levels (odds ratio 15.41) versus low baseline IL‐17A and BD‐2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib. Conclusion: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL‐23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib. [ABSTRACT FROM AUTHOR]

ObjectivesTo describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use.MethodsPatients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time.ResultsWe studied 1700 patients with a mean (s.d.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis.ConclusionGCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.

Objective. To address suboptimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a five-year disease-specific cardiovascular risk prediction model. Methods. We analyzed data from a prospective cohort of participants with PsD without a history of cardiovascular events. Traditional cardiovascular risk factors and PsD-related measures of disease activity were considered as potential predictors. The study outcome included nonfatal and fatal cardiovascular events. A base prediction model included 10 traditional cardiovascular risk factors. Eight PsD-related factors were assessed by adding them to the base model to create expanded models, which were controlled for PsD therapies. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression with 10-fold cross-validation. Model performance was assessed using measures of discrimination and calibration and measures of sensitivity and specificity. Results. Between 1992 and 2020, 85 of 1,336 participants developed cardiovascular events. Discrimination of the base model (with traditional cardiovascular risk factors alone) was excellent, with an area under the receiver operator characteristic curve (AUC) of 85.5 (95% confidence interval [CI] 81.9–89.1). Optimal models did not select any of the tested disease-specific factors. In a sensitivity analysis, which excluded lipid lowering and antihypertensive treatments, the number of damaged joints was selected in the expanded model. However, this model did not improve risk discrimination compared to the base model (AUC 85.5, 95% CI 82.0–89.1). Conclusion. Traditional cardiovascular risk factors alone are effective in predicting cardiovascular risk in patients with PsD. A risk score based on these factors performed well, indicating excellent discrimination and calibration. [ABSTRACT FROM AUTHOR]

Introduction: The phase 3 DISCOVER-2 trial evaluated the effect of guselkumab on impaired work productivity and nonwork activity in biologic-naïve patients with psoriatic arthritis (PsA).Methods: Adults with active PsA were randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks (Q8W), or placebo (with crossover to guselkumab Q4W at week 24). Least squares mean change from baseline in Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) domains and employment were assessed by treatment group. Multivariate analysis of data from weeks 0 through 24 assessed independent associations between PsA clinical features and WPAI-PsA domains.Results: In total, 738 patients were evaluated (guselkumab Q4W n = 245; guselkumab Q8W n = 248; placebo n = 245). At week 24, improvements (reduced impairment) in presenteeism (Q4W -20.1%, Q8W -19.6%, placebo -10.5%), work productivity (Q4W -20.1%, Q8W -19.2%, placebo -10.6%), and nonwork activity (Q4W -20.5%, Q8W -21.2%, placebo -9.9%) were greater in guselkumab-treated versus placebo-treated patients. At week 52, following placebo crossover at week 24, improvements were similar among groups. Baseline absenteeism was minimal and did not change in any group. By week 52, 23.1-25.9% of guselkumab-treated patients who were unemployed at baseline were employed. All WPAI-PsA domains were positively associated with C-reactive protein level, fatigue, and pain. All domains except absenteeism were positively associated with enthesitis and Psoriasis Area and Severity Index score. Age was negatively associated with presenteeism and work productivity loss, female sex and tender joint count were positively associated with nonwork activity impairment, and dactylitis was positively associated with presenteeism.Conclusion: Both guselkumab regimens reduced work productivity loss and nonwork activity impairment in patients with active PsA. Association of work productivity loss and nonwork activity impairment with PsA joint and skin features suggests that improvement in both features is beneficial for optimizing improved work productivity loss and nonwork activity impairment.Trial Registration: ClinicalTrials.gov identifier, NCT03158285. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to assess the effectiveness of conventional and targeted disease-modifying antirheumatic drugs (cDMARDs and tDMARDs, respectively) in treating enthesitis in psoriatic arthritis (PsA).Methods: Patients with active enthesitis, defined as ≥ 1 tender entheses (of the 29 enthesis sites included in the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Leeds Enthesitis Index, and the Maastricht Ankylosing Spondylitis Enthesitis Score), who were enrolled in a large PsA cohort were included. Medications at baseline were classified into 3 mutually exclusive categories: (1) no treatment or nonsteroidal antiinflammatory drugs (NSAIDs) only; (2) cDMARDs ± NSAIDs; and (3) tDMARDs ± cDMARDs/NSAIDs. Complete resolution of enthesitis (no tender enthesis) at 12 months was the primary outcome. Logistic regression models were developed to determine the association between medication category and enthesitis resolution.Results: Of the 1270 patients studied, 628 (49.44%) had enthesitis. Of these, 526 patients (51.71% males; mean [SD] age 49.02 [13.12] years; mean enthesitis score 2.13 [2.16]; median enthesitis score 2 [IQR 1-2]), with adequate follow-up were analyzed. Complete resolution of enthesitis was noted in 453 (86.12%) patients, within a mean period of 8.73 (3.48) months from baseline. In the regression analysis, though not significant, DMARDs (categories II and III) had higher odds ratios (ORs) compared to category 1 for resolution of enthesitis. Enthesitis resolution was associated with lower joint activity (OR 0.97, 95% CI 0.95-0.99; P = 0.01) and male sex (OR 1.66, 95% CI 0.97-2.84; P = 0.06).Conclusion: Resolution of enthesitis was observed in 86% of patients in an observational setting regardless of the medication used. Future effectiveness studies may warrant evaluation of enthesitis using advanced imaging. [ABSTRACT FROM AUTHOR]